Therapeutic effect of presurgical treatment with longacting octreotide (Sandostatin® LAR®) in patients with acromegaly.

INTRODUCTION: The aim of this study was to assess the therapeutic effect and the safety of pre-surgical treatment with long-acting octreotide in patients with acromegaly. MATERIAL AND METHODS: This project was conducted in 25 centres across Poland as a non-interventional, multicentre, observational study in patients with acromegaly, in which long-acting octreotide Sandostatin® LAR®) was administered before surgery. They were 148 patients included into the study: 88 females and 60 males aged 18-86 years (51.3 ± 13.4). RESULTS: Eighty patients completed the study (underwent tumour surgery). The CRF included: baseline visit, four follow-up visits every three months before surgery, and two follow-up visits every three months after surgery. Sandostatin® LAR® was administered every four weeks. The efficacy measures were as follows: change of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, number of patients fulfilling criteria of cure, and change of adenoma (micro- and macroadenomas) size during the treatment. Normalisation of GH and IGF-1 concentrations were obtained in 42.4 and 49.1% of patients at the end of medical therapy, respectively. Normalisation of GH and IGF-1 concentrations were obtained in 77.9 and 83.8% of patients after surgery, respectively. Reduction of microadenoma size was documented in 58.8% of patients, and in 70% of patients with macroadenomas at the end of medical therapy. In 74.0% of patients no pituitary tumour was shown on MRI after surgery. CONCLUSION: We have shown good surgical outcome in patients with acromegaly after pre-treatment with somatostatin analogue, and good tolerance and safety of the therapy, supporting the national recommendation for pre-surgical treatment with long-acting somatostatin analogues in acromegaly patients.

The association between FTO gene polymorphism rs9939609 and obesity is sex-specific in the population of PURE study in Poland.

BACKGROUND: Fat mass and obesity-associated gene (FTO) polymorphism remains the strongest known genetic determinant of common obesity. However, its influence depends on ethnicity, and the FTO-mediated predisposition to other metabolic disturbances is questionable. OBJECTIVES: The aim of our study was to evaluate the association between FTO rs9939609 polymorphism and metabolic syndrome in a population of Prospective Urban Rural Epidemiology (PURE) study in Poland. MATERIAL AND METHODS: We enrolled 1,097 participants of the PURE study (683 women and 414 men) from the Lower Silesian voivodeship. Anthropometrical parameters and blood pressure were measured. Blood samples were taken for an examination of lipid profile and fasting glucose level. Genomic DNA was isolated and FTO polymorphism rs9939609 was genotyped. RESULTS: Male A-allele carriers had significantly higher mean body mass, body mass index (BMI), waist-to-hip ratio (WHR), and waist and hip circumferences than men without risk allele. They were also more often diagnosed with obesity on the basis of BMI and central obesity parameters. No such influence was observed in women. There were no significant associations between FTO polymorphism and metabolic syndrome or its components. CONCLUSIONS: Our results suggest a sex-specific association between FTO polymorphism and obesity traits. The occurrence of metabolic syndrome or its components was not related with FTO gene variation in our cohort.

Determinants of obesity in population of PURE study from Lower Silesia.

INTRODUCTION: The knowledge about obesity pathogenesis is insufficient. The aim of our study was to investigate environmental and individual determinants of obesity in population of PURE study from Lower Silesia. MATERIAL AND METHODS: This was a cross sectional observation of 1064 inhabitants of Wroclaw and neighbouring rural area (671 women, 393 men), who took part in PURE study in years 2007-2010. Each participant answered PURE questionnaire and International Physical Activity Questionnaire providing information about obesity risk factors. Anthropometric measurements were collected, blood samples were taken for assessment of FTO gene polymorphism. A stepwise logistic regression analysis was performed to identify the most significant predictors of obesity. RESULTS: 31% of the study group had obesity (BMI over 30 kg/m², no difference between men and women), overweight (BMI 25-29.9 kg/m²) affected 48.1% of men and 36.7% of women. Determinants of obesity in female group were: rural inhabitancy, chronic medication, unemployment, age, sedentary leisure time activity, non-smoking, hypertension in family, family related stress (p = 0.66 in the Hosmer-Lemeshow test). Determinants of obesity in male group were rural inhabitancy, chronic medication, family related stress, diabetes in family (p = 0.27 in the Hosmer-Lemeshow test). Risk factors for central obesity were similar, however in women oral contraception and physical activity were associated with lower obesity risk. CONCLUSIONS: Environmental factors, especially rural inhabitancy and family related stress were associated with higher obesity risk in our study. Employment, smoking, physical activity and use of oral contraception seemed to have protective role in women.

Serum Lipid Transfer Proteins in Hypothyreotic Patients Are Inversely Correlated with Thyroid-Stimulating Hormone (TSH) Levels.

BACKGROUND Plasma cholesteryl ester transfer protein (CETP) activity is often decreased in patients with hypothyroidism, whereas less is known about the phospholipid transfer protein (PLTP). We aimed to evaluate simultaneously serum CETP and PLTP activity in patients diagnosed with hypothyroidism. MATERIAL AND METHODS The selection criteria for control group members (without thyroid dysfunction) in this case to case study were levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides similar to those in study group patients (101 patients diagnosed with hypothyroidism). Serum CETP and PLTP activities were measured by homogenous fluorometric assays using synthetic donor particle substrates. RESULTS Serum CETP and PLTP activities in hypothyreotic patients were lower (p<0.001) compared with those in healthy subjects. This lowering was associated with significant changes in HDL-C subclasses: decrease in HDL2- and increase in HDL3 cholesterol levels. Multiple linear regression analyses adjusted for age, sex, body mass index, smoking habits, and alcohol drinking showed a strong association between hypothyroidism and activity of lipid transfer proteins. A linear inverse relationship between thyroid-stimulating hormone (TSH) and CETP (r=-0.21; p<0.01) and between TSH and PLTP (r=-0.24; p<0.001) was shown. There also was a positive correlation (p<0.001) between CETP and HDL2 cholesterol (r=0.27) and between PLTP and HDL2 cholesterol (r=0.37). A negative correlation between CETP and HDL3 cholesterol (r=-0.22: p<0.01) and between PLTP and HDL3 cholesterol (r=-0.24; p<0.001) has been demonstrated as well. CONCLUSIONS The decreased HDL2 and increased HDL3 cholesterol levels in subjects with hypothyroidism are consequences of decreased activity of lipid transfer proteins. These changes are early symptoms of lipid disturbances in hypothyroidism.

Interdisciplinary Aspects of Primary Hyperparathyroidism: Symptomatology in a Series of 100 Cases.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder. Beside renal and skeletal complications, it has a wide variety of nonspecific symptoms from other organs that mimic other diseases and delay the diagnosis. In recent decades the clinical profile of PHPT has evolved to less symptomatic forms. OBJECTIVES: The aim of the study was to revise the symptomatology profile of PHPT in a single region, and to facilitate early PHPT diagnosis by encouraging interdisciplinary communication among medical professionals. MATERIAL AND METHODS: Data from 100 patients (94 women and 6 men, aged 57.1 ± 13.7 years) diagnosed with PHPT in the authors' center during the past decade were retrospectively analyzed. Biochemical conditions and clinical manifestations (renal, skeletal, cardiovascular, gastrointestinal and asymptomatic) were evaluated. RESULTS: Renal symptoms were present in 55% of the patients. In the course of unrecognized disease, seven lithotripsy procedures, seven surgical lithotomy procedures and two nephrectomies were performed. Osteoporosis/ /osteopenia was present in 66% and 10% of the study group, respectively. In 16% there were fragility fractures; in 10% brown tumors were present, and 55% of the PHPT patients were hypertensive. Gastrointestinal symptoms were present in 52%; pancreatitis was documented in 3%. PHPT was diagnosed incidentally in asymptomatic patients in 15% of the group. Mean serum Ca was 2.87 mmol/L (SD: 0.36), mean urine Ca was 15.97 mEq/24 h (SD: 7.89), mean serum PTH was 324 pg/mL (SD 425.21). The duration from the appearance of any symptom to the diagnosis varied from < 1 year (19%), 1-10 years (46%) to > 10 years (35%). CONCLUSIONS: PHPT is still diagnosed too late, after a period of untreated symptomatic disease. Multidisciplinary cooperation among specialists on the diagnostic level can help avoid late complications of unrecognized disease.

Evaluation of Selected Atherosclerosis Risk Factors in Women with Subclinical Hypothyroidism Treated with L-Thyroxine.

BACKGROUND: Subclinical hypothyroidism (SCH) is a common endocrine disorder, probably increasing cardiovascular (CV) risk. However, the relation between SCH and atherosclerosis risk factors remains unclear. OBJECTIVES: The aim of the study was to evaluate selected atherosclerosis risk factors in women with SCH in comparison to a group of healthy women and women with overt hypothyroidism, as well as to investigate the influence of L-thyroxine replacement on those risk factors. MATERIAL AND METHODS: The study group consisted of 187 obese women aged between 50 and 70 years: 100 women with SCH, 45 women with overt hypothyroidism and 42 women with TSH level in reference ranges. Anthropometric parameters were evaluated. Laboratory tests included thyroid hormones concentrations, lipid profile with apolipoproteins, CRP, homocysteine. Atherosclerotic indexes were calculated: LDL C/HDL C ratio, apoA1/apoB ratio and Castelli risk index. Women with hypothyroidism were given L-thyroxine treatment and after 6 months in euthyroidism the evaluation was repeated. RESULTS: Total cholesterol, LDL-cholesterol and triglycerides concentrations as well as LDL-C/HDL-C ratio and Castelli index were higher in SCH than in controls and decreased after L-thyroxin substitution. All of the calculated atherosclerosis indexes showed significant positive correlations with TSH concentration in SCH group. Also in this group the systolic and diastolic blood pressure decreased significantly after treatment. CONCLUSIONS: Dyslipidemia in obese SCH women is not severe, but if untreated for many years, it may lead to atherosclerosis. Substitution therapy improves the lipid profile, changing the relations between protective and proatherogenic fractions of serum lipids, and optimises blood pressure.

The Frequencies of Haplotypes of FTO Gene Variants and Their Association with the Distribution of Body Fat in Non-Obese Poles.

BACKGROUND: The minor allele frequencies (MAFs) of the FTO gene vary substantially among different ethnic groups, and this variation may explain, to some degree, the differences between estimates of the effects of these alleles on body fat distribution indicators. OBJECTIVES: The aim of this study was to investigate the prevalence of fat mass and obesity associated (FTO) gene variants characterizing the structure of FTO haplotypes in a large Polish population, and to examine the influence of FTO gene variants on body fat distribution among metabolically obese normal weight (MONW) individuals, i.e. those with a normal BMI and visceral obesity. MATERIAL AND METHODS: A total of 854 non-obese individuals aged from 20 to 40 years, residing in three different regions in Poland, were studied. All the patients from this group were genotyped for four FTO gene variants (rs9939609, rs9930506, rs1421085 and rs1121980). Simultaneous identification of all single nucleotide polymorphisms (SNPs) was conducted using the minisequencing method with a pair of designed specific primers. RESULTS: Over 90% of the diplotypes contain only the two most common haplotypes, in three combinations of haplotype pairs: CTAT/CTAT comprised 26.9% in women and 30.9% in men; CTAT/TCGA comprised 45.0% in women and 44.4% in men; and TCGA/TCGA comprised 19.3% in woman and 14.8% in men. The analysis of the variance in body fat distribution parameters shows no statistically significant differences between the three common haplotype pairs in either men or women. CONCLUSIONS: The young Polish population is characterized by two disparate haplotypes of common FTO gene variants: TCGA (a risk SNP haplotype), and CTAT (a protective haplotype). No significant differences were found between fat distribution indicators in relation to haplotypes in either women and men.

Vitamin D receptor gene polymorphisms in Alzheimer's disease patients.

THE AIM: The aim of this study was to determine whether polymorphisms of the VDR gene may increase the risk of Alzheimer disease (AD) development in Lower Silesian patients in comparison with other populations. MATERIAL AND METHODS: 108 AD patients (aged 73.7±8.6) vs 77 healthy volunteers (aged 64.5±7.8) in the Lower Silesian population were studied. We investigated the frequency of the VDR polymorphisms rs731236 (TaqI), rs7975232 (ApaI), rs10735810 (FokI) and rs1544410 (BsmI) in the AD group vs the healthy group. Afterwards, MEDLINE and ResearchGate were studied to compare our investigation with other populations, due to the relatively small group size in our study. RESULTS: We did not observe any significant differences in frequency of genotypes of rs731236 (TaqI), rs10735810 (FokI) or rs1544410 (BsmI) VDR polymorphisms between the two Lower Silesian groups. Frequency of allele A of ApaI in the control group was significantly higher vs AD patients (p<0.0177) in the Lower Silesian population. Furthermore the difference in the occurrence of allele t in TaqI and allele A in ApaI between AD patients vs the control group was significant (respectively p<0.0056, p<0.0140) in British Europeans. This observation may suggest that allele "a" of the ApaI polymorphism is a risk allele in AD Lower Silesian patients. We compared our results with those obtained for the population of British Europeans. In multivariate stepwise regression, allele "A" of ApaI was associated with 30% lower risk of AD (OR=0.70, p=0.0009) in total treated Polish and British populations. We did not observe similar results in Turkish and Iranian populations. CONCLUSION: Our data suggest that the allele "A" VDR genotype of ApaI reduces AD risk, probably depending on ethnic origin and climatic conditions.

Current and emerging therapies for adrenocortical carcinoma--review.

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Patients may present with hormone excess or a local mass effect. The most common imaging techniques (CT and MRI) use both size and appearance to distinguish between benign and malignant tumors. Open surgery by an expert surgeon with R0 target is the treatment of choice. Mitotane (alone or in combination with cytotoxic drugs) may be administered after surgery or in patients not amenable to surgery. The role of radiotherapy as an adjuvant treatment is uncertain whereas targeted radionuclide therapy seems to be a promising option. New adjuvant treatment options, even after complete tumor removal, are desired because postoperative disease-free survival at 5 yrs is only around 30%. The establishment of detailed guidelines with the purpose of optimizing therapy with only mitotane but also in combination with other antineoplasmatic drugs is still a task to be done. Future advances in the management of ACC will probably be connected with better understanding of the molecular pathogenesis.

Usefulness of Somatostatin Receptor Scintigraphy (Tc-[HYNIC, Tyr3]-Octreotide) and 123I-Metaiodobenzylguanidine Scintigraphy in Patients with SDHx Gene-Related Pheochromocytomas and Paragangliomas Detected by Computed Tomography.

AIMS: The aim of this study was to assess the usefulness of somatostatin receptor scintigraphy (SRS) using (99m)Tc-[HYNIC, Tyr3]-octreotide (TOC) and 123I-metaiodobenzylguanidine (mIBG) in patients with SDHx-related syndromes in which paragangliomas were detected by computed tomography and to establish an optimal imaging diagnostic algorithm in SDHx mutation carriers. METHODS: All carriers with clinical and radiological findings suggesting paragangliomas were screened by SRS and 123I-mIBG. Lesions were classified by body regions, i.e. head and neck, chest, abdomen with pelvis and adrenal gland as well as metastasis. RESULTS: We evaluated 46 SDHx gene mutation carriers (32 index cases and 14 relatives; 28 SDHD, 16 SDHB and 2 SDHC). In this group, 102 benign tumors were found in 39 studied patients, and malignant disease was diagnosed in 7 patients. In benign tumors, the sensitivity of SRS was estimated at 77% and of 123I-mIBG at 22.0%. The SRS and mIBG sensitivity was found to be clearly region dependent (p < 0.001). The highest SRS sensitivity was found in head and neck paragangliomas (HNP; 91.4%) and the lowest was found in abdominal paragangliomas and pheochromocytomas (40 and 42.9%, respectively). The highest 123I-mIBG sensitivity was found in pheochromocytomas (sensitivity of 100%) and the lowest in HNP (sensitivity of 3.7%). In metastatic disease, SRS was superior to mIBG (sensitivity of 95.2 vs. 23.8%, respectively). CONCLUSION: SRS and 123I-mIBG single photon emission computed tomography (SPECT) sensitivity in SDHx patients is highly body region dependent. In malignant tumors, SRS is superior to 123I-mIBG SPECT.

Challenges in the diagnosis of pheochromocytoma and paraganglioma syndrome.

OBJECTIVES: Adrenal pheochromocytomas are rare neuroendocrine tumours, however their prevalence is probably underestimated - in some series 50% were diagnosed at autopsy. The clinical presentation varies among patients, that is why diagnosis might be difficult to establish. Pheochromocytoma may coexist with paraganglioma and when paraganglioma is diagnosed, the patient should be screened for pheochromocytoma too, especially in people with hypertension. We present a case of woman with pheochromocytoma, but diagnosed after incidence of stroke, who had also paraganglioma in the past. Additionally, a teratoma was diagnosed simultaneously. CASE REPORT: 49-year old woman with hypertension was referred to the Department of Endocrinology, Diabetology and Isotope Therapy in Wroclaw with suspected pheochromocytoma. She was operated twice because of paraganglioma of the right and left carotid artery, second operation was complicated with stroke. After administration of anticoagulants a bleeding from gastrointestinal tract occurred. During diagnostic process CT of the abdomen showed tumour in the right adrenal gland and a tumour in pelvis. Significantly elevated catecholamines and their metabolites in blood and urine confirmed the diagnosis of pheochromocytoma. Both tumours were removed surgically, the second was teratoma maturum. Genetic screening for hereditary pheochromocytoma was proceeded. A mutation in SDHD gene was revealed in patient's DNA and subsequently in blood samples of her sister and daughter. CONCLUSIONS: Occurrence of paraganglioma with hypertension suggest need of screening for pheochromocytoma-paraganglioma syndrome, especially in case of paragangliomas in family history. Early treatment is crucial to avoid life-threatening cardiovascular complications. The association between pheochromocytoma and teratoma is unclear.

The role of fat mass and obesity-associated gene (FTO) in obesity - an overview.

Obesity is an epidemic of the 21st century. The magnitude of this problem stems from its increasing prevalence and numerous metabolic complications caused by excessive fat accumulation. The pathogenesis involves both environmental and genetic factors, and FTO (fat mass and obesity-associated gene) is one of the most significant among genes predisposing to obesity. The role of FTO polymorphism in the development of obesity has been confirmed in many studies, but the effect varies significantly in different ethnic groups. Moreover, the exact mechanisms of FTO influence are yet to be explained. The association between FTO and lifestyle factors such as diet and physical activity has been extensively studied in recent years. This paper presents current knowledge about the role of FTO gene in the development of obesity and type 2 diabetes in different ethnic groups and the association between FTO polymorphism and lifestyle modifications predisposing to adiposity.

[Thyroid dysfunction in patients treated with tyrosine kinase inhibitors]. / Zaburzenia funkcji tarczycy u chorych leczonych inhibitorami kinaz tyrozynowych.

Tyrosine kinase Inhibitors are relatively new drugs used for treatment of several malignancies. The treatment is generally well tolerated, incidence of side effects of significant intensity is low. Hypothyroidism is a frequent complication, the mechanism and guidelines on endocrine treatment remain controversial. Observations indicate that hypothyroidism during treatment is correlated with higher probability of better response to treatment. Further research is necessary to establish guidelines on thyroid function tests and indications for treatment of hypothyroidism.

Accumulation of abdominal fat in relation to selected proinflammatory cytokines concentrations in non-obese Wroclaw inhabitants.

INTRODUCTION: Metabolically obese normal weight (MONW) subjects, despite their normal BMI, present metabolic disturbances characteristic of abdominal obesity. One of the reasons might be subclinical inflammation caused by the fat tissue excess. The aim of this study was to assess the association between the accumulation of fat (especially abdominal) and the concentration of selected proinflammatory cytokines - interleukins (IL-6, IL-18) and C-reactive protein (CRP). MATERIAL AND METHODS: The study population consisted of 342 subjects (218 women, 124 men; age 20-40 years, BMI < 27 kg/m2) recruited from a community centre in Wroclaw. The group was divided based on the homeostasis assessment insulin resistance index (HOMA) value: 90 MONW subjects with HOMA > 1.69 and 252 subjects as control group. Anthropometric parameters, serum IL-6, IL-18, CRP, glucose, insulin concentrations and insulin sensitivity/resistance indexes were evaluated. RESULTS: CRP levels were significantly higher (3.26 vs. 1.97, p = 0.03) in MONW women than in the control group. Serum IL-6, IL-18 levels in males and females did not differ in both groups. IL-6 showed a significant correlation with the abdominal to gynoidal fat tissue deposit ratio in women. There were correlations between the CRP and BMI, WHR, waist circumference, total fat, abdominal fat deposit, and abdominal to gynoidal fat deposit ratio in both sexes. In women, positive correlations between CRP and HOMA, FIRI and negative with QUICKI index were present. CONCLUSIONS: Increased accumulation of abdominal adipose tissue in non-obese, young and healthy subjects is related to increased CRP levels.

Subclinical Cushing's syndrome in adrenal incidentalomas--possible metabolic consequences.

INTRODUCTION: The presence of subclinical Cushing's syndrome (SCS) and some features of the metabolic syndrome were evaluated in adrenal incidentaloma patients. MATERIAL AND METHODS: 165 patients were studied. Plasma cortisol, ACTH, DHEA-S, 17-OH-P, aldosterone, renin activity and 24-h urinary methoxycatecholamines were measured. Fasting concentrations of glucose, insulin, triglycerides, T-chol., HDL-chol. and LDL-chol. were determined and the FIRI and QUICKI indices were calculated. Blood pressure, WHR and BMI were determined in all patients. Forty healthy volunteers were the controls. RESULTS: 133 patients had unchanged endocrine function, 32 demonstrated hormonal disturbances without clinical symptoms (in 26 nonclinical hypercortisolism). The WHR and blood pressure in the SCS group were significantly higher than in the patients with nonfunctioning adenoma (NA). T-chol and LDL-chol were significantly higher, but HDL-chol was significantly lower, in the SCS than in the NA patients. Fasting insulin level was significantly higher in the SCS than in the NA patients and controls, while fasting glucose level was comparable. QUICKI was significantly lower in the SCS and NA patients than in the controls, while FIRI was significantly higher in the SCS group. CONCLUSIONS: In incidentaloma patients, hormonal function of the adrenal gland should be estimated because some of them present subclinical hyperfunction. These patients frequently display features of metabolic syndrome such as insulin resistance, hypertension, high triglycerides, T-chol and LDL-chol levels. Subtle autonomous cortisol secretion may be the cause of these features.

Primary hyperparathyroidism presenting as a giant cell tumor of the jaws.

OBJECTIVE: Giant cell tumors of the maxillofacial skeleton are uncommon, they are usually late manifestation of primary hyperparathyroidism. A series of five clinical cases in four women and one man presenting as the giant cell lesions in the maxilla and/or mandible are discussed. METHODS: Biopsy of the lesions, biochemical and hormonal analyses, densitometry and parathyroid scintigraphy were carried out. RESULTS: Biopsy of the lesions showed giant cell tumor of bone. The medical history and laboratory analyses showed primary hyperparathyroidism. Bone density loss was documented and scintigraphy revealed the presence of parathyroid adenomas in four cases. Surgical treatment of hyperparathyroidism, and in the second step - after 6-12 months - the subsequent excision of residual brown tumors in all cases was performed. CONCLUSIONS: One should have in mind that osteolytic bone lesions may be due to metabolic disease of the bone. Accurate diagnosis enabling the proper treatment should be carried out, avoiding unnecessary harm to the patients.

Left ventricular function impairment in patients with normal-weight obesity: contribution of abdominal fat deposition, profibrotic state, reduced insulin sensitivity, and proinflammatory activation.

BACKGROUND: Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities. METHODS AND RESULTS: One hundred sixty-eight subjects (age, 38±7 years) with BMI <25kg/m(2) and no history of any disease affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (ß=-0.17, P<0.006), C-reactive protein (ß=-0.20, P<0.002) and abdominal fat deposit (ß=-0.20, P<0.003); for tissue S velocity, PICP (ß=-0.21, P<0.002) and abdominal fat deposit (ß=-0.43, P<0.0001); for tissue E velocity, abdominal fat deposit (ß=-0.30, P<0.0001), PICP (ß=-0.31, P<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; ß=-0.20, P<0.002); and for E/e'-PICP, IL-18 (both ß=0.18, P<0.01) and HOMA IR (ß=0.16, P<0.04). CONCLUSIONS: In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.

Genetic aspects of pheochromocytoma.

Pheochromocytomas are derived from chromaffin cells of the adrenal medulla which synthesize and secrete catecholamines, thus affecting the cardiovascular system and metabolic processes. Pheochromocytoma is a tumor of the following multicarcinoma hereditary syndromes: type 2 multiple endocrine neoplasia, von Hippel-Lindau disease, type 1 neurofibromatosis and the pheochromocytomas/paragangliomas syndrome. Pheochromocytomas are relatively rare, and because of non-specific manifestation of these tumors and the possible lack of signs and symptoms for extended periods of time, the diagnosis may be delayed, which may, in turn, lead to death. Pheochromocytomas may occur sporadically. However, due to the frequent incidence of hereditary forms of these cancers, the presymptomatic genetic testing of family members with a positive family history is indicated, thus allowing for selecting people with higher risk of cancer. Early detection of the syndrome and the coexisting tumors (which may be malignant) may lead to a correct diagnosis, regular surveillance, preventive examinations and implementation of appropriate early treatment. Recent examinations have shown significant involvement of RET, VHL, NF1, SDHB and SDHD as well as the newly discovered KIF1Bß, TMEM127 and MAX genes in pathogenesis of these tumors. The microarray-gene expression studies, based on the analysis of cellular pathways, have revealed two distinct clusters indicating two different routes of tumorgenesis. The genotype-phenotype correlations are still being studied and future research can give us clearer information about the function of these genes, which may prove crucial from the clinical point of view.

Evaluation of the prevalence of metabolic obesity and normal weight among the Polish population.

INTRODUCTION: In the 1980s, the idea evolved that some individuals with normal weight (Metabolically Obese, Normal-Weight), who probably have increased abdominal fat, have metabolic disturbances related to obesity. This observation initiated the concept of the metabolically obese but normal-weight syndrome (MONW). Since then, there have been only a few studies in non-obese subjects. MONW men and women should be regarded as at high risk for cardiovascular disease. MATERIAL AND METHOD: A group of 854 randomly chosen non-obese men and women, 20-40 years of age, was selected from three different areas of Poland - Szczecin, Krakow and Wroclaw. All subjects were interviewed and underwent physical examination, anthropometric measurements (waist circumference, hip circumference, BMI and WHR) as well as densitometry (total body DPX, total fat, android/gynoid deposit). Serum level of fasting glucose and insulin, indices of insulin sensibility (QUICKI) and insulin resistance (HOMA, FIRI), total cholesterol, triglycerides and HDL-C were measured using commercially available kits. LDL-C level was calculated using Friedewald's formula. RESULTS: The total amassed fatty tissue and its android deposit was found to be significantly greater in MONW men and women. MONW women were found to exhibit increased levels of triglycerides and LDL-C but lower levels of HDL-C. In women with excess abdominal fat (EAF), fasting glucose and insulin levels, HOMA and FIRI were considerably higher, while QUICKI was lower. Triglyceride and LDL-C levels were also higher while HDL-C levels were lower. In men with EAF, increased levels of total cholesterol and LDL-C were confirmed. CONCLUSIONS: The occurrence of MONW is contingent upon the diagnosis criterion and increases when the criterion represents the value of HOMA - 21.76% in women and 31.42% in men. The frequency of MONW occurrence is lower when the criterion for abdominal fat content limit is used, amounting to 15.78% in women and 7.83% in men.

Pro12Ala PPAR γ2 gene polymorphism in PCOS women: the role of compounds regulating satiety.

UNLABELLED: Five to ten percent of women of reproductive age suffer from polycystic ovary syndrome (PCOS). Leptin, NPY, galanin, cholecystokinin (CCK) are involved in the regulation of eating behavior. PPARγ are receptors that are probably involved in hyperandrogenism. This study was designed to assess associations between the Pro12Ala PPARγ2 gene polymorphism and satiety factors in PCOS. Fifty-four PCOS women and 51 healthy women were studied. Leptin, NPY, galanin, CCK levels, and genetic studies to detect Pro12Ala PPARγ2 gene polymorphism were assessed. The leptin levels in the PCOS women carrying Pro12Ala genotype were higher than in those with Pro12Pro and Ala12Ala. The PCOS women had higher leptin and NPY levels and lower galanin levels. Obese PCOS patients had lower CCK levels. CONCLUSIONS: In the PCOS women, a single Ala allele may have a protective role as far as hyperleptinemia is concerned. The PCOS women may reveal a disrupted central leptin/NPY feedback loop with some shifts in food intake.